TITLE:
Review. Comparative structures and evolution of mammalian lipase I (LIPI) genes and proteins: A close relative of vertebrate phospholipase LIPH
AUTHORS:
Roger S. Holmes, Laura A. Cox
KEYWORDS:
Mammalian LIPI Genes and Proteins; Amino Acid Sequence; Lipase I; Evolution; Phylogeny
JOURNAL NAME:
Natural Science,
Vol.4 No.12A,
December
31,
2012
ABSTRACT:
Lipase I (enzyme name LIPI or LPDL) (gene name LIPI [human] or Lipi
[mouse]) is a phospholipase which generates 2-acyl lysophosphatidic acid (LPA),
a lipid mediator required for maintaining homeostasis of diverse biological functions
and in activating cell surface recaptors. Bioinformatic methods were used to predict
the amino acid sequences, secondary and tertiary structures and gene locations
for LIPI genes and encoded proteins using data from several mammalian genome
projects. LIPI is located on human chromosome 21 and is distinct from other
phospholipase A1-like genes (LIPH and PS-PLA1). Mammalian LIPI genes contained
10 (human) or 11 (mouse) coding exons transcribed predominantly on the negative
DNA strand. Mammalian LIPI protein subunits shared 61% - 99% sequence
identities and exhibited sequence alignments and identities for key LIPI amino
acid residues as well as extensive conservation of predicted secondary and
tertiary structures with those previously reported for pancreatic lipase (PL),
with “N-signal peptide”, “lipase” and “plat” structural domains. Comparative
studies of mammalian LIPI sequences with LIPH, PS-PLA1 and pancreatic lipase
(PL) confirmed predictions for LIPI N-terminal signal peptides (residues 1 - 15);
predominantly conserved mammalian LIPI N-glycosylation sites (63NNSL and
396NISS for human LIPI); active site “triad” residues (Ser159; Asp183; His253);
disulfide bond residues (238 - 251; 275 - 286; 289 - 297; 436 - 455); and a 12 residue “active site lid”, which is shorter than
for other lipases examined. Phylogenetic analyses supported a hypothesis
that LIPI arose from a vertebrate LIPH gene duplication event within a
mammalian common ancestral genome. In addition, LIPI, LIPH and PL-PLA1 genes
were distinct from the vascular lipase (LIPG, LIPC and LPL) and pancreatic lipase
(PL) gene families.